title: Renal clearance and intestinal generation of p-cresyl sulfate and indoxyl sulfate in CKD.
abstract: OBJECTIVE
  p-Cresyl sulfate and indoxyl sulfate contribute to cardiovascular disease and progression of renal disease. Renal clearance of both solutes mainly depends on tubular secretion, and serum concentrations are widely dispersed for any given stage of CKD. From this information, it is inferred that estimated GFR is not a suitable proxy of the clearance of these solutes. Formal clearance studies have, however, not been performed to date.
  
  
  METHODS
  This study analyzed renal clearances of p-cresyl sulfate and indoxyl sulfate in the Leuven CKD cohort (NCT00441623; inclusion between November of 2005 and September of 2006) and explored their relationship with estimated GFR. Multivariate linear regression models were built to evaluate contributions of estimated GFR, demographics, and generation rates to p-cresyl sulfate and indoxyl sulfate serum concentrations.
  
  
  RESULTS
  Renal clearances were analyzed in 203 patients with CKD stages 1-5. Indoxyl sulfate clearances (median=17.7, interquartile range=9.4-33.2 ml/min) exceeded p-cresyl sulfate clearances (median=6.8, interquartile range=3.4-12.0 ml/min) by about threefold. A linear relationship was observed between estimated GFR and clearances of p-cresyl sulfate (R(2)=0.50, P<0.001) and indoxyl sulfate (R(2)=0.55, P<0.001). In multivariate regression, p-cresyl sulfate concentrations were associated (R(2)=0.75) with estimated GFR and generation rate (both P<0.001). Indoxyl sulfate concentrations were associated (R(2)=0.74) with estimated GFR, generation rate (both P<0.001), age (P<0.05), and sex (P<0.05).
  
  
  CONCLUSIONS
  Estimated GFR provides an acceptable estimate of renal clearance of p-cresyl sulfate and indoxyl sulfate. Remarkably, clearances of indoxyl sulfate exceed clearances of p-cresyl sulfate by approximately threefold, suggesting substantial differences between tubular transporter affinities and/or involvement of separate transporter systems for p-cresyl sulfate and indoxyl sulfate.
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Poesen
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Viaene
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.forename: Bert
authors.initials: B
authors.lastname: Bammens
authors.forename: Ben
authors.initials: B
authors.lastname: Sprangers
authors.forename: Maarten
authors.initials: M
authors.lastname: Naesens
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers; D003408:Cresols / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007200:Indican / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012737:Sex Factors; D013463:Sulfuric Acid Esters / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican